Browse
Submit Data
Databases
API
Help

Dataset Information

402 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human EGFR AP-MS project - Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress

ABSTRACT: Mass spectrometry was applied to comprehensively analyze the phosphorylation, ubiquitination, and interactome of wild type and endocytosis-defective EGFR variants before and after internalization in response to EGF or stress.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Jiefei Tong

LAB HEAD: Mike Moran

PROVIDER: PXD000788 | Pride | 2014-10-23

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Proteomic analysis of the epidermal growth factor receptor (EGFR) interactome and post-translational modifications associated with receptor endocytosis in response to EGF and stress.

Tong Jiefei J Taylor Paul P Moran Michael F MF

Molecular & cellular proteomics : MCP 20140505 7

Aberrant expression, activation, and stabilization of epidermal growth factor receptor (EGFR) are causally associated with several human cancers. Post-translational modifications and protein-protein interactions directly modulate the signaling and trafficking of the EGFR. Activated EGFR is internalized by endocytosis and then either recycled back to the cell surface or degraded in the lysosome. EGFR internalization and recycling also occur in response to stresses that activate p38 MAP kinase. Ma ...[more]

PMID: 24797263

Similar Datasets

Differential gene expression analysis of U87MG EGFRvA cells vs. U87MG EGFR cells

Project description:EGFRvA is a novel and widely-expressed EGFR isoform, whose upregulation is positively related to glioma grades. Intriguingly, it is the upregulation of EGFRvA but not EGFR that significantly correlates with a poor prognosis in glioma patients. Cancer cells expressing EGFRvA (relative to EGFR) display a higher invasive capacity and a lower sensitivity to EGFR tyrosine kinase inhibitors (TKIs). To investigate the significant differently expressed genes between U87MG EGFRvA cells and U87MG EGFR cellsM-oM-<M-^Lmicroarray experiments were conducted. Gene-expression profiling was performed on the CapitalBio 35k human Genome Array microchips (Beijing, China).

2012-09-30 | E-GEOD-41230 | biostudies-arrayexpress

RNF41 regulation of the dendritic cell receptor Clec9A

Project description:The dendritic cell receptor Clec9A facilitates processing of dead cell-derived antigens for cross-presentation and the induction of effective CD8+ T cell immune responses. This study investigates the role of E3 ubiquitin ligase RNF41 in Clec9A-mediated ubiquitination, and Clec9A-interactions.

2020-11-27 | PXD018926 | Pride

The multivalency of the glucocorticoid receptor ligand-binding domain explains its manifold physiological activities

Project description:The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. Although numerous crystal structures of the GR ligand-binding domain (GR-LBD) have been reported, the functional oligomeric state of the full-length receptor, which is essential for its transcriptional activity, remains disputed. Here we present five new crystal structures of agonist-bound GR-LBD, along with a thorough analysis of previous structural work. Biologically relevant homodimers were identified by studying a battery of GR point mutants including crosslinking assays in solution and quantitative fluorescence microscopy in live cells. Our results highlight the relevance of non-canonical dimerization modes for GR, especially of contacts made by loop L1-3 residues such as Tyr545. Our work unveils likely pathophysiologically relevant quaternary assemblies of the nuclear receptor with important implications for glucocorticoid action and drug design.

2023-03-11 | PXD028039 | Pride

The strutural dynamics of EGFR Exon 19 mutants

Project description:Tyrosine kinase inhibtors are used to treat non-small cell lung cancers (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations in the tyrosine kinase domain (TKD). We characterized the dynamics of purified EGFR exon 19 kinase domain mutants by HDX-MS with or withour erlotinib, one of the first-generation TKIs.

2023-03-11 | PXD037448 | Pride

N-Glycosylation of the Epidermal Growth Factor Receptor (EGFR) Derived from Human Oral Squamous Carcinoma Cells with beta-Catenin/CREB-Binding Protein (CBP) Inhibition

Project description:Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world; oral squamous cell carcinomas (OSCC) account for the majority of HNSCC cases. A major driver of OSCC is the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK) with 12 N-glycosylation sites whose activity is aberrantly upregulated in 80-90% of tumors. EGFR antennary-fucosylated glycans have been shown to suppress EGFR dimerization and signaling in lung adenocarcinoma. High levels of fucosylated glycan epitopes have also been observed in OSCC, but invasive regions lose expression of linkage-specific fucosylated epitopes, suggesting that certain fucosylated glycans are involved in the suppression of cell growth and invasion. We found that EGFR from metastatic HSC-3 cells has low levels of fucosylated N-glycans, while EGFR from non-metastatic CAL27 cells shows higher levels of fucosylation at multiple EGFR glycosylation sites including sites N420 and N579, via nUPLC-MS/MS. In cell culture and in mouse tumor xenografts, treatment with ICG-001, a small molecule inhibitor of the interaction between nuclear -catenin and CREB-binding protein (CBP) resulted in higher expression of FUT2 and FUT3, higher fucosylation of EGFR at sites N420 and N579, and decreased EGFR abundance. In addition, we have performed in-depth characterization of multiply-fucosylated N-glycans via glycopeptide tandem mass spectrometry to understand which fucosylated glycan epitopes are involved in the observed effect.

2020-03-26 | PXD017060 | Pride

Biochemical and Structural Basif for Differential Inhibitor Sensitivity of EGFR with Distinct Exon 19 Mutaions

Project description:Tyrosine kinase inhibitors (TKIs) are used to treat non-small cell lung cancers (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations in the tyrosine kinase domain (TKD). We studied structural basis of differential TKI sensitivity among EGFR exon 19 mutants by HDX-MS.

2023-03-11 | PXD037374 | Pride

DDX3X associated proteins with or without circRIG-I

Project description:We use FLAG pulldown assay to find DDX3X associated proteins with or without circRIG-I in HEK293T.

2022-11-16 | PXD037929 | Pride

Proteomic analysis of serum EVs derived from PSC, CCA and PSC-CCA patients

Project description:Cholangiocarcinomas (CCAs) are heterogeneous biliary cancers with dismal prognosis. Their etiologies remain mostly unclear, although primary sclerosing cholangitis (PSC) is a well-known risk factor. There is an urgent need of accurate non-invasive biomarkers for early CCA diagnosis and to predict patient´s prognosis, which may improve their clinical management and outcome. Here, by high-throughput proteomic analysis of serum extracellular vesicles (EVs), we identified diagnostic and/or prognostic biomarkers specific for CCAs in patients with PSC, and others common to all CCA subtypes. Bulk RNA tissue transcriptomic data revealed that these biomarkers are predominantly expressed in hepatobiliary tissues, being expressed in different liver cell types. Furthermore, single-cell RNAseq (scRNA-seq) analysis revealed that the expression of these biomarkers was preferentially found in malignant cholangiocytes within CCA tumors. In summary, these results highlight the potential of serum EVs to reflect cancer presence, especially for difficult-to-diagnose malignancies, including CCA."

2023-07-20 | PXD026197 | Pride

Identification of MDN1-dependent proteome changes in Arabidopsis seeds

Project description:mdn1-1 is a weak mutant of the Arabidopsis MDN1 gene. mdn1-1 exhibits an increased seed-size phenotype. To further figure out the proteome changes in the mdn1-1 seeds, we applied the iTRAQ-based LC-MS/MS analysis. A total of 3217 proteins were identified in dry seeds of both wild type and mdn1-1. The significantly differentially expressed proteins (DEPs) were filtered out based on the fold change (FC > 1.5 or < 0.667) of expression level and P value (< 0.05). We defined 282 up- and 40 downregulated proteins in mdn1-1.

2019-11-12 | PXD013784 | Pride

Predictive data-driven modeling of C-terminal tyrosine function in the EGFR signaling network

Project description:The Epidermal Growth Factor Receptor (EGFR) has been studied extensively due to its critical role in cellular signaling and association with disease. Previous models have elucidated interactions between EGFR and downstream adaptor proteins, or showed phenotypes affected by EGFR. However, the link between EGFR phosphorylation and phenotypic outcome is still poorly understood. Here, we employed a suite of isogenic cells lines expressing site-specific mutations at each of the EGFR C-terminal phosphorylation sites to interrogate their role in signaling network and cell biological response to stimulation. Our results demonstrate the resilience of the EGFR network, which was largely similar even in the context of multiple Y-to-F mutations in the EGFR C-terminal tail, while also revealing nodes in the network that have not previously been linked to EGFR signaling. Our data-driven model highlights signaling network nodes associated with distinct EGF-driven cell responses, including migration, proliferation, and receptor trafficking. Application of this same approach to less studied RTKs should provide a plethora of novel associations that should lead to a much better understanding of these signaling networks.

2023-05-09 | PXD032403 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data